Prediction of early pregnancy outcome
File(s)
Author(s)
Abdallah, Yazan
Type
Thesis
Abstract
Introduction: Conventional ultrasound has been used in the management of early
pregnancy complications. Common clinical situations that are encountered include
pregnancies of unknown location (PUL) defined as a woman with a positive
pregnancy test, but when no intra or extra-uterine pregnancy is visualised on transvaginal
sonography (TVS); intra-uterine pregnancies of uncertain viability (IPUV)
defines as when an intrauterine gestational sac (<20mm mean diameter) is seen on
ultrasonography with no visible yolk sac or embryo, or an embryo of <7mm crown–
rump length with no visible heart activity; and recurrent pregnancy losses (RPL).
Emerging evidence suggests that novel strategies may be developed to predict early
pregnancy complications such as miscarriage using B mode ultrasound imaging and
advanced three-dimensional 3D technology, alongside early pregnancy biochemical
parameters. These strategies can be assessed prior to conception, at implantation
and subsequently in the early stages of pregnancy. In this thesis we describe a
series of studies to evaluate the role of ultrasound and biochemical markers for the
prediction of early pregnancy complications in relation to these three time periods.
Methods: Pre-conception, we used 3D ultrasound to study longitudinal changes in
endometrial morphology and vascularity, the influence of physical injury to the
endometrium on these parameters and their relationship with implantation success.
We investigated the relationship between the ovulation-implantation (OI) time interval
and subsequent implantation or early pregnancy failure. Post-conception, we studied
PUL and IPUV. In the PUL group, ultrasonography in combination with serum
biochemical markers were used to validate the role of mathematical logistic
regression models for predicting pregnancy location and viability. We investigated
the performance of biochemical markers in urine to assess whether measurements
of urine markers can replace serum markers for the management of PUL. In the
IPUV group, we established ultrasound criteria that can be used to definitively
diagnose miscarriage. In addition, we studied the growth of these pregnancies and
its relationship with pregnancy viability and the appearance of early embryonic
structures in the gestational sac.
Results: We have provided evidence to support the view that endometrial biopsy
enhances endometrial vascularity in women with a history of RPL. We have
suggested a safe approach to characterise PUL and have shown that logistic
regression-based prediction models can reliably be used and further developed to
predict the outcome in PUL, independent of the timing of serum biochemistry. In
addition, we have shown a potential role for urine pregnancy biochemistry in the
management of PUL. We have developed new reliable definitions to diagnose
miscarriage, which have now been adopted both in the UK and internationally.
Furthermore, we found that, gestation sac growth is not a safe indicator of pregnancy
viability, although cutoff values for embryo growth can be suggested below which a
miscarriage can be predicted.
Conclusion: The studies described in this thesis have introduced a number of novel
findings in relation to the use of ultrasound and biochemistry for predicting, and
optimising the management of, early pregnancy complications from the
preconception phase, through early implantation, to the post conception phase.
pregnancy complications. Common clinical situations that are encountered include
pregnancies of unknown location (PUL) defined as a woman with a positive
pregnancy test, but when no intra or extra-uterine pregnancy is visualised on transvaginal
sonography (TVS); intra-uterine pregnancies of uncertain viability (IPUV)
defines as when an intrauterine gestational sac (<20mm mean diameter) is seen on
ultrasonography with no visible yolk sac or embryo, or an embryo of <7mm crown–
rump length with no visible heart activity; and recurrent pregnancy losses (RPL).
Emerging evidence suggests that novel strategies may be developed to predict early
pregnancy complications such as miscarriage using B mode ultrasound imaging and
advanced three-dimensional 3D technology, alongside early pregnancy biochemical
parameters. These strategies can be assessed prior to conception, at implantation
and subsequently in the early stages of pregnancy. In this thesis we describe a
series of studies to evaluate the role of ultrasound and biochemical markers for the
prediction of early pregnancy complications in relation to these three time periods.
Methods: Pre-conception, we used 3D ultrasound to study longitudinal changes in
endometrial morphology and vascularity, the influence of physical injury to the
endometrium on these parameters and their relationship with implantation success.
We investigated the relationship between the ovulation-implantation (OI) time interval
and subsequent implantation or early pregnancy failure. Post-conception, we studied
PUL and IPUV. In the PUL group, ultrasonography in combination with serum
biochemical markers were used to validate the role of mathematical logistic
regression models for predicting pregnancy location and viability. We investigated
the performance of biochemical markers in urine to assess whether measurements
of urine markers can replace serum markers for the management of PUL. In the
IPUV group, we established ultrasound criteria that can be used to definitively
diagnose miscarriage. In addition, we studied the growth of these pregnancies and
its relationship with pregnancy viability and the appearance of early embryonic
structures in the gestational sac.
Results: We have provided evidence to support the view that endometrial biopsy
enhances endometrial vascularity in women with a history of RPL. We have
suggested a safe approach to characterise PUL and have shown that logistic
regression-based prediction models can reliably be used and further developed to
predict the outcome in PUL, independent of the timing of serum biochemistry. In
addition, we have shown a potential role for urine pregnancy biochemistry in the
management of PUL. We have developed new reliable definitions to diagnose
miscarriage, which have now been adopted both in the UK and internationally.
Furthermore, we found that, gestation sac growth is not a safe indicator of pregnancy
viability, although cutoff values for embryo growth can be suggested below which a
miscarriage can be predicted.
Conclusion: The studies described in this thesis have introduced a number of novel
findings in relation to the use of ultrasound and biochemistry for predicting, and
optimising the management of, early pregnancy complications from the
preconception phase, through early implantation, to the post conception phase.
Version
Open Access
Date Issued
2013-10
Date Awarded
2014-07
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Ghaem-Maghami, Sadaf
Publisher Department
Department of Surgery and Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)